Genomic Variations in ATP7B Gene in Indian Patients with Wilson Disease.

OBJECTIVE: To report genotype data of the patients with Wilson disease (WD) hailing from across several parts of India to add to the available spectrum of causative variants in ATP7B gene (ATPase copper transporting beta polypeptide gene) and associated phenotypes in the Indian population. METHODS: The entire ATP7B gene was sequenced in 58 patients with WD and additional testing was also done by MLPA to look for intragenic deletions duplications and exome sequencing to rule out genetic variations with similar phenotypic overlap. RESULTS: Of all patients, 37 patients had a total of 33 distinct pathogenic variations, including 29 in the exonic regions and 4 at intronic splice sites. Of the variations identified, six were novel. The underlying genomic variations could be identified in nearly two-thirds of the patients by sequencing the entire gene. CONCLUSIONS: This study reports the genotype-phenotype data to add to the available spectrum of causative variants in ATP7B gene. The inability to detect a pathogenic variation in some patients and the existence of phenotypic variations in individuals with the same variation suggest that additional factors or genes may play a role in causation of the disease. Further, a marked genetic heterogeneity was found in the study patients, indicating ethnic diversity of the Indian population.

Triple Diagnosis of Crohn's Disease, Celiac Disease, and Eosinophilic Esophagitis in a Child With Siderius-Hamel Syndrome.

Siderius-Hamel syndrome is a rare condition characterized by intellectual disability and distinct facial features. Crohn's disease-related eosinophilic esophagitis (EoE) has been reported; however, an association between celiac disease and EoE remains controversial. We present a case of a child with Siderius-Hamel syndrome who had characteristic findings of all these conditions-Crohn's disease, celiac disease, and EoE-an occurrence that to our knowledge has not been reported previously. The purpose of this report is to make physicians aware of this rare occurrence, so that it can be kept in mind while evaluating a patient with Siderius-Hamel syndrome presenting with gastrointestinal complaints.

Prevalence of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Cross-Sectional, Clinicoepidemiological, Multicenter, Nationwide Study in India: The PREDICT Study.

BACKGROUND: The study aimed at assessing the prevalence and clinical profile of minimal hepatic encephalopathy (MHE) in patients with cirrhosis using neuropsychological assessment and at understanding the management practices of MHE in the Indian clinical setting. METHODS: This cross-sectional, clinicoepidemiological study conducted at 20 sites enrolled liver cirrhosis patients with Grade 0 hepatic encephalopathy according to West-Haven Criteria. Patients were subjected to mini-mental state examination and those with a score of ≥24 were assessed using psychometric hepatic encephalopathy score. Short Form-36 questionnaire was administered to assess the impact on health-related quality of life. RESULTS: Of the 1260 enrolled patients, 1114 were included in the analysis. The mean age was 49.5 years and majority were males (901 [81%]). The prevalence of MHE was found to be 59.7% (665/1114) based on the psychometric hepatic encephalopathy score of ≤-5. Alcohol-related liver disease was the most common etiology (482 [43.27%]) followed by viral infection (239 [21.45%]). Past smokers as well as those currently smoking were more likely to have MHE than nonsmokers. A significant association was found between tobacco chewing, smoking, alcohol consumption, diabetes, and the presence of MHE. Multivariable analysis revealed smoking as the only parameter associated with MHE. A total of 300 (26.9%) patients were on prophylaxis with lactulose/lactitol or rifaximin. These patients were less likely to have MHE as compared to those not on prophylaxis (odds ratio, 0.67; 95% confidence interval, 0.50-0.88; P = 0.005). CONCLUSION: The disease burden of MHE is quite substantial in patients with cirrhosis with no apparent cognitive defect. Smoking, whether past or current, has significant association with the presence of MHE. Although MHE has been shown to adversely affect quality of life, prophylaxis for MHE is not routinely practiced in the Indian setting.The study has been registered under clinical trials registry of India (CTRI/2014/01/004306).

Eosinophilic gastroenteritis: Atypical cause for chronic diarrhea in human immunodeficiency virus-associated immunosuppression.

Eosinophilic gastroenteritis (EGE) is an uncommon disease in both immunocompetent and immunocompromised. We describe a 57-year-old male with human immunodeficiency virus who presented to us with chronic diarrhea. He had no history of allergies and had significant weight loss, normal systemic examination, and a complete blood count showing no eosinophilia. After an esophagogastroduodenoscopy, the diagnosis of EGE was made by histopathological findings. The symptoms started improving with the initiation of treatment with oral prednisolone.

Pyoderma Gangrenosum-A New Manifestation of Wilson Disease?

Seventeen year old girl, a known case of Wilson disease presented to us with a non-healing skin ulcer followed by appearance of jaundice, ascites and progressive fatigue of 1 month duration. She was diagnosed to have Wilson disease 5 years back and had been well controlled on d-penicillamine. On enquiry, she was found to be noncompliant with her medication in the preceding 6 months. On examination, she had severe pallor, icterus with moderate ascites and oedema feet. Investigations revealed severe haemolytic anemia and deranged liver function. The lesion was diagnosed to be pyoderma gangrenosum on skin biopsy. The appearance of a cutaneous lesion followed by deterioration in the liver disease and hemolysis suggested uncontrolled Wilson disease as the triggering factor. Chelation therapy improved her haemoglobin and liver function as well as led to healing of the ulcer. We describe pyoderma gangrenosum as a new manifestation of Wilson disease.

Primary Liver Sinusoidal Non-Hodgkin's Lymphoma Presenting as Acute Liver Failure.

We describe a case of a middle-aged woman, who presented to us with fever, anorexia, abdominal distension from a massive hepatomegaly, low hemoglobin, and acute liver failure. A liver biopsy revealed B cell non-Hodgkin's lymphoma predominantly in the sinusoids with CD10, CD20, and Bcl-2 positive on immunohistochemistry. She initially responded well to chemotherapy but succumbed 6 months later to the recurrence of disease. Sinusoidal non-Hodgkin's lymphoma of the liver should be considered in the differential diagnosis of a patient with large hepatomegaly presenting with acute liver failure.

Chronic diarrhea--an unusual presentation of metastatic invasive lobular cancer of breast.

We report a 56-year-old lady with chronic diarrhea and weight loss. She had undergone lumpectomy with axillary clearance (node positive) four years ago for invasive lobular carcinoma of breast. Investigations revealed involvement of almost the entire gut with skip areas. Biopsies from the stomach showed presence of signet-ring cells, suggestive of metastases from invasive lobular carcinoma of breast. Estrogen receptor immuno-staining was positive, confirming the diagnosis. She was treated initially with octreotide and later with chemotherapeutic agents, with transient relief in diarrhea. She succumbed eight months later.